Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

Abstract

Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.

Keywords:

• neural stem cells
• small extracellular vesicles
• ischemic stroke
• neuroprotection
• neural regeneration

Abbreviations

NSCs, Neural stem cells; NSC-sEVs, Neural stem cell-derived small extracellular vesicles; sEVs, Small extracellular vesicles; BBB, Blood-brain barrier; tPA, Tissue-type plasminogen activator; MSCs, Mesenchymal stem cells; BDNF, Brain-derived neurotrophic factor; VEGF, Vascular endothelial growth factor; SVZ, Subventricular zone; SGZ, Subgranular zone; DG, Dentate gyrus; CNS, Central nervous system; miRNAs, microRNAs; MAPK, Mitogen-activated protein kinase; RGD, Arg-Gly-Asp.

Acknowledgments

We thank Fig.Draw (https://www.figdraw.com/) for editing figures.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This work was funded by the National Key R&D Program of China (2022YFA1104900 & 2022YFA1104904), the National Natural Science Foundation of China (82171459), the Department of Education of Guangdong Province (2021ZDZX2011).